The purpose of this project is to investigate two principal problems: a) the nature of the chemical modifications which leads to the formation and accumulation of altered enzyme and protein molecules in cells of senescent organisms; b) the functional consequences of this accumulation in cells and tissues of aging animals. It has been shown in our laboratory that the majority of enzymes tested exhibit altered forms in a variety of organs and cell types in aging nematodes, mice and rats. The altered enzyme molecules show reduced catalytic activity and changed temperature sensitivity. The alterations do not involve large differences or apparent changes in antigenicity of proteins. The alterations mainly involve post-translational modifications of the proteins. Amino acid substitutions due to miscoding are apparently inconsequential to this phenomenon. It has been found that there is a slow down in protein degradation in cells of senescent nematodes and mice. This slow down is at least partially responsible for the accumulation of faulty proteins. The nature of the defect in the degradation system is currently being studied. The postulate that this defect may interfere with the normal functions of the degradation system, i.e., supply of amino acids during starvation and disposal of altered proteins, is currently being studied.